Alcohol use disorders exact a substantial toll on America's public health especially with respect to brain structure and its myriad functions. The goal of this proposal is to increase understanding of the nature and potential mechanisms of alcoholism-induced brain injury using advanced magnetic resonance brain imaging that could guide rehabilitation strategies and inform treatment development. Current concepts of diseases of the brain suggest that different diseases affect specific neurocircuitry connecting disparate reaches of the brain. Converging evidence from human in vivo and postmortem studies of chronic alcoholism strongly implicate disruption of frontocerebellar circuitry as a principal contributor to the characteristic pattern of alcoholism-related impairment. Although animal studies have identified the neuroanatomy of cerebrocerebellar circuits relevant to alcoholism, recent human neuroimaging experiments have demonstrated functional cerebrocerebellar circuitry that does not necessarily have a known neuroanatomy. These intrinsic connectivity networks (ICN) can be identified with in vivo functional connectivity MR imaging (fcMRI). In addition to examining the known cerebrocerebellar anatomy, identification of intrinsic neurocircuitry could provide basic science insight into mechanisms underlying selective impairments and fundamental information for developing behavioral or pharmacological therapies and approaches for improving processing efficiency and compensation for associated dysfunction. The goal of this hypothesis-driven proposal is to determine the integrity of cerebrocerebellar ICNs, their functional significance, and the influence of alcohol-induced neuropathology on these networks. The three specific aims are: Specific Aim 1: To elucidate the status of intrinsic and activated functional cerebellar networks using resting state fcMRI and task-activated fMRI Specific Aim 2: To determine the impact of alcoholism-induced degradation of the neuroanatomy (identified with MRI and diffusion tensor imaging, DTI) and cerebral blood perfusion (measured with arterial spin labeling, ASL) on task-activated and intrinsic connectivity networks involving frontocerebellar circuitry Specific Aim 3: To examine the motor and cognitive ramifications of intrinsic network status identified with fcMRI. PUBLIC HEALTH RELEVANCE: Alcohol use disorders exact a substantial toll on America's public health especially as it affects the brain and its many functions. The goal of this proposal is to increase the understanding of the nature and potential biological mechanisms of alcoholism-induced brain injury, which may well contribute to difficulties in achieving and maintaining sobriety. Advanced magnetic resonance brain imaging used to specify where alcoholic injury occurs in the brain and how injury impairs function should guide insights for rehabilitation strategies and treatment development.